Circulating extracellular histones are elevated in CM. (A) Circulating histone levels measured in the serum of healthy controls (HC; n = 22), and patients with mild febrile illness (MF; n = 34), uncomplicated malaria (UM; n = 50), aparasitemic non-CM coma (Non-CM; n = 10) and admission serum from children who met the standard WHO case definition of CM at presentation (n = 218). Thick black lines and error bars are the geometric mean and 95% CI. (B) Refining the diagnosis of CM by retinal examination, comparison is made between circulating histone levels in children with Ret⁻CM (n = 48) and Ret⁺CM (n = 170). (C-F) Scatter plots to examine the correlation between histone levels and plasma factors in children with Ret⁺CM are shown. (C) Plasma fibrin monomer levels; (D) prothrombin fragment F1+2; (E) OPG; and (F) whole blood peripheral parasite density. (C-E) Data shown were measured by ELISA, and parasite density was calculated from white blood cell–normalized slide counts using thick smears. Comparison was made using ANOVA and Dunnett’s multiple comparison test (A), Student t test (B), and Pearson's correlation coefficient (C-F). Non-CM are aparasitemic children with encephalopathy in a coma due to a cause other than malaria.